In this study, bis-carbonyl podand (triethylene glycol bis(2-carbonylphenyl)ether) ( 1 ) was synthesized from the reaction of triethylene glycol dichloride with salicylaldehyde. Then, Schiff base podans ( 2 and 3 ) were prepared from the interaction of bis(carbonyl) podand with 2-amino-4-methylphenol and 2-amino3-hydroxypyridine in ethanol medium. The structures of podands have been investigated by elementary analysis, FT-IR, UV-Vis,H- 1-NMR, C-13-NMR and MS spectroscopy. The antimicrobial activities of the podands have been investigated for their minimum inhibitory concentration (MIC) to bacteria and yeast cultures. Furthermore, the interactions of Schiff base podands with DNA were investigated by UV-Vis spectra and gel electrophoresis method. The efficiency of molecules in DNA cleavage has also been investigated by computational examination of the interaction between Schiff base podands and human topoisomerase II alpha (hTop alpha) enzyme by molecular docking method. Docking results of podands were compared with known topo inhibitors. UV-Vis spectroscopy studies of the interactions between the podands and calf thymus DNA (CT-DNA) showed that the compounds interact with CT-DNA via electrostatic binding. DNA cleavage study showed that the podands cleaved DNA oxidatively. It has been observed that especially podand 2 shows the best interactions with the hTop alpha's binding site by molecular docking method compared to known inhibitors. In addition, antioxidant activities of Schiff base podands were measured using the DPPH method. Podands showed similar antioxidant activity with BHT. It was also found that activity increased with increasing concentration of compounds. In addition, the anion recognition ability of all Schiff bases was examined by colorimetric, UV-Vis and fluorescence spectroscopy. Schiff base podand 2 showed a visually and spectroscopically detectable color and absorbance change against fluoride, cyanide and hydroxyl anions, while Schiff base podand 3 showed the same change against fluoride, cyanide, acetate, dihydrogen phosphate and hydroxyl anions. No significant color and absorbance change were observed upon addition of other anions such as bromide, iodide, thiocyanate, perchlorate, and hydrogen sulphate.(c) 2022 Elsevier B.V. All rights reserved.